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Androgen action via testicular arteriole smooth muscle cells is important for Leydig cell function, vasomotion and testicular fluid dynamics.

Welsh M, Sharpe RM, Moffat L, Atanassova N, Saunders PT, Kilter S, Bergh A, Smith LB - PLoS ONE (2010)

Bottom Line: Androgens control vasomotion, but how they exert these effects remains unclear.However, seminiferous tubule lumen volume was reduced in adult SMARKO males while interstitial volume was increased, perhaps indicating altered fluid dynamics; this was associated with compensated Leydig cell failure.In conclusion, these results indicate that ablating arteriole smooth muscle AR does not grossly alter spermatogenesis or affect male fertility but does subtly impair Leydig cell function and testicular fluid exchange, possibly by locally regulating microvascular blood flow within the testis.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, Edinburgh, United Kingdom.

ABSTRACT
Regulation of blood flow through the testicular microvasculature by vasomotion is thought to be important for normal testis function as it regulates interstitial fluid (IF) dynamics which is an important intra-testicular transport medium. Androgens control vasomotion, but how they exert these effects remains unclear. One possibility is by signalling via androgen receptors (AR) expressed in testicular arteriole smooth muscle cells. To investigate this and determine the overall importance of this mechanism in testis function, we generated a blood vessel smooth muscle cell-specific AR knockout mouse (SMARKO). Gross reproductive development was normal in SMARKO mice but testis weight was reduced in adulthood compared to control littermates; this reduction was not due to any changes in germ cell volume or to deficits in testosterone, LH or FSH concentrations and did not cause infertility. However, seminiferous tubule lumen volume was reduced in adult SMARKO males while interstitial volume was increased, perhaps indicating altered fluid dynamics; this was associated with compensated Leydig cell failure. Vasomotion was impaired in adult SMARKO males, though overall testis blood flow was normal and there was an increase in the overall blood vessel volume per testis in adult SMARKOs. In conclusion, these results indicate that ablating arteriole smooth muscle AR does not grossly alter spermatogenesis or affect male fertility but does subtly impair Leydig cell function and testicular fluid exchange, possibly by locally regulating microvascular blood flow within the testis.

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Testicular response to hCG exposure in SMARKO mice.A. Testis weight increased significantly in SMAR control, but not in SMARKO 16 hours after hCG treatment, presumably reflecting alterations in interstitial fluid volume. B. Serum testosterone concentrations increased significantly in both SMARKO and control adult males after exposure to hCG, but this increase was larger in controls than in KOs. C. Interstitial fluid testosterone concentrations were significantly higher in control testes than in SMARKOs at d100 after exposure to hCG. D. Average blood flow (Pfu) through adult SMARKO and control testes 16 hours after exposure to hCG. E. Average vasomotion frequency in adult SMARKO and control testes 16 hours after exposure to hCG. F. Average vasomotion amplitude in adult SMARKO and control testes 16 hours after exposure to hCG. Note that vasomotion frequency and amplitude were only measured in the two hcg-treated controls testes in which vasomotion could still be detected. Values are mean ± SEM (n = 5–7 mice), * p<0.05, ** p<0.01, *** p<0.001, compared to control littermates. a p<0.01, compared to untreated mice.
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pone-0013632-g008: Testicular response to hCG exposure in SMARKO mice.A. Testis weight increased significantly in SMAR control, but not in SMARKO 16 hours after hCG treatment, presumably reflecting alterations in interstitial fluid volume. B. Serum testosterone concentrations increased significantly in both SMARKO and control adult males after exposure to hCG, but this increase was larger in controls than in KOs. C. Interstitial fluid testosterone concentrations were significantly higher in control testes than in SMARKOs at d100 after exposure to hCG. D. Average blood flow (Pfu) through adult SMARKO and control testes 16 hours after exposure to hCG. E. Average vasomotion frequency in adult SMARKO and control testes 16 hours after exposure to hCG. F. Average vasomotion amplitude in adult SMARKO and control testes 16 hours after exposure to hCG. Note that vasomotion frequency and amplitude were only measured in the two hcg-treated controls testes in which vasomotion could still be detected. Values are mean ± SEM (n = 5–7 mice), * p<0.05, ** p<0.01, *** p<0.001, compared to control littermates. a p<0.01, compared to untreated mice.

Mentions: It is well documented that exposure to hCG increases blood vessel permeability and inhibits vasomotion resulting in increased IF volume in adult rats [20], [39], [40], [41]. In this study, exposure to hCG 16 h prior to cull resulted in a significant increase in testis weight in adult control mice, reflecting increased IF volume, but not in SMARKO adults (Figure 8A). hCG also significantly increased serum testosterone concentrations in both SMARKO and controls (Figure 8B), however, there was only a 3-fold increase in SMARKO mice compared to a 7-fold increase in control mice. IF testosterone concentrations were significantly increased in control mice after hCG exposure, compared to SMARKOs (Figure 8C). Exposure to hCG prevented vasomotion in 71% of control adult mice (5 of 7 males) and prevented vasomotion in all SMARKO adult mice (5 of 5 males). This lack of vasomotion in hCG treated control or SMARKO mice resulted in a small but not significant increase in testicular blood flow (Figure 8D). Vasomotion frequency and amplitude were both significantly reduced in the two hCG-treated control mice in which vasomotion persisted (Figure 8E and F).


Androgen action via testicular arteriole smooth muscle cells is important for Leydig cell function, vasomotion and testicular fluid dynamics.

Welsh M, Sharpe RM, Moffat L, Atanassova N, Saunders PT, Kilter S, Bergh A, Smith LB - PLoS ONE (2010)

Testicular response to hCG exposure in SMARKO mice.A. Testis weight increased significantly in SMAR control, but not in SMARKO 16 hours after hCG treatment, presumably reflecting alterations in interstitial fluid volume. B. Serum testosterone concentrations increased significantly in both SMARKO and control adult males after exposure to hCG, but this increase was larger in controls than in KOs. C. Interstitial fluid testosterone concentrations were significantly higher in control testes than in SMARKOs at d100 after exposure to hCG. D. Average blood flow (Pfu) through adult SMARKO and control testes 16 hours after exposure to hCG. E. Average vasomotion frequency in adult SMARKO and control testes 16 hours after exposure to hCG. F. Average vasomotion amplitude in adult SMARKO and control testes 16 hours after exposure to hCG. Note that vasomotion frequency and amplitude were only measured in the two hcg-treated controls testes in which vasomotion could still be detected. Values are mean ± SEM (n = 5–7 mice), * p<0.05, ** p<0.01, *** p<0.001, compared to control littermates. a p<0.01, compared to untreated mice.
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Related In: Results  -  Collection

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pone-0013632-g008: Testicular response to hCG exposure in SMARKO mice.A. Testis weight increased significantly in SMAR control, but not in SMARKO 16 hours after hCG treatment, presumably reflecting alterations in interstitial fluid volume. B. Serum testosterone concentrations increased significantly in both SMARKO and control adult males after exposure to hCG, but this increase was larger in controls than in KOs. C. Interstitial fluid testosterone concentrations were significantly higher in control testes than in SMARKOs at d100 after exposure to hCG. D. Average blood flow (Pfu) through adult SMARKO and control testes 16 hours after exposure to hCG. E. Average vasomotion frequency in adult SMARKO and control testes 16 hours after exposure to hCG. F. Average vasomotion amplitude in adult SMARKO and control testes 16 hours after exposure to hCG. Note that vasomotion frequency and amplitude were only measured in the two hcg-treated controls testes in which vasomotion could still be detected. Values are mean ± SEM (n = 5–7 mice), * p<0.05, ** p<0.01, *** p<0.001, compared to control littermates. a p<0.01, compared to untreated mice.
Mentions: It is well documented that exposure to hCG increases blood vessel permeability and inhibits vasomotion resulting in increased IF volume in adult rats [20], [39], [40], [41]. In this study, exposure to hCG 16 h prior to cull resulted in a significant increase in testis weight in adult control mice, reflecting increased IF volume, but not in SMARKO adults (Figure 8A). hCG also significantly increased serum testosterone concentrations in both SMARKO and controls (Figure 8B), however, there was only a 3-fold increase in SMARKO mice compared to a 7-fold increase in control mice. IF testosterone concentrations were significantly increased in control mice after hCG exposure, compared to SMARKOs (Figure 8C). Exposure to hCG prevented vasomotion in 71% of control adult mice (5 of 7 males) and prevented vasomotion in all SMARKO adult mice (5 of 5 males). This lack of vasomotion in hCG treated control or SMARKO mice resulted in a small but not significant increase in testicular blood flow (Figure 8D). Vasomotion frequency and amplitude were both significantly reduced in the two hCG-treated control mice in which vasomotion persisted (Figure 8E and F).

Bottom Line: Androgens control vasomotion, but how they exert these effects remains unclear.However, seminiferous tubule lumen volume was reduced in adult SMARKO males while interstitial volume was increased, perhaps indicating altered fluid dynamics; this was associated with compensated Leydig cell failure.In conclusion, these results indicate that ablating arteriole smooth muscle AR does not grossly alter spermatogenesis or affect male fertility but does subtly impair Leydig cell function and testicular fluid exchange, possibly by locally regulating microvascular blood flow within the testis.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, Edinburgh, United Kingdom.

ABSTRACT
Regulation of blood flow through the testicular microvasculature by vasomotion is thought to be important for normal testis function as it regulates interstitial fluid (IF) dynamics which is an important intra-testicular transport medium. Androgens control vasomotion, but how they exert these effects remains unclear. One possibility is by signalling via androgen receptors (AR) expressed in testicular arteriole smooth muscle cells. To investigate this and determine the overall importance of this mechanism in testis function, we generated a blood vessel smooth muscle cell-specific AR knockout mouse (SMARKO). Gross reproductive development was normal in SMARKO mice but testis weight was reduced in adulthood compared to control littermates; this reduction was not due to any changes in germ cell volume or to deficits in testosterone, LH or FSH concentrations and did not cause infertility. However, seminiferous tubule lumen volume was reduced in adult SMARKO males while interstitial volume was increased, perhaps indicating altered fluid dynamics; this was associated with compensated Leydig cell failure. Vasomotion was impaired in adult SMARKO males, though overall testis blood flow was normal and there was an increase in the overall blood vessel volume per testis in adult SMARKOs. In conclusion, these results indicate that ablating arteriole smooth muscle AR does not grossly alter spermatogenesis or affect male fertility but does subtly impair Leydig cell function and testicular fluid exchange, possibly by locally regulating microvascular blood flow within the testis.

Show MeSH
Related in: MedlinePlus